The Research Plan describes a series of experiments which will examine how spatial information is processed in the mammalian brain. In previous studies a population of neurons was identified within the hippocampal formation and anterior thalamic nuclei which discharge as a function of the animal's head direction, independent of the animal's behavior and spatial location. This spatial signal provides a model system for examining how primary sensory information, entering through various sensory pathways, is transformed into a "higher level cognitive signal" representing the organism's spatial relationship with its environment. The mechanisms which accomplish this transformation in the central nervous system are not known. The first aim of the proposal is to examine how the head direction (HD) cell signal is processed in the brain. To address this issue, four experimental approaches are pursued: anatomical, single-unit recordings, lesion studies, and electrical stimulation. During the proposed project period, we will focus on understanding the contributions of the following brain areas to the HD cell signal: anterior thalamic nuclei, lateral mammillary nuclei, retrosplenial cortex, and the dorsal tegmental area. A second line of investigation will focus on how animals use HD cells during navigation and spatial tasks. Specifically, we will determine what types of internal sensory systems (vestibular, kinesthetic, optic flow) are involved in path integration and whether each system alone is sufficient to support path integration. Additional experiments will determine 1) whether particular brain areas are critical for path integration, 2) the extent to which episodic spatial information can be encoded and retrieved without a hippocampus, and 3) how lesions of the directional system affect hippocampal place cell discharge. Finally, we will explore if and how HD cell activity guides an animal's behavior in both working and reference memory tasks and in more complex navigational tasks that require path integration for successful performance. The results from the proposed experiments will provide insight into how spatial information is processed in the brain and have implications for human health and behavior. It is common for elderly patients and patients with Alzheimers disease, a disease often associated with marked pathology in limbic system structures, to experience spatial disorientation to the extent that constant supervision is required. Learning how spatial information is processed in the rat brain will give us clues about the complex nature of spatial processes in humans.